公开(公告)号：US20200055838A1

公开(公告)日：2020-02-20

申请号：US16487385

申请日：2018-02-12

Applicant: SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

Inventor： Youhong HU ,  Meiyu GENG ,  Wenming REN ,  Jian DING ,  Xiaocong GUAN ,  Jing AI ,  Lang WANG ,  Xia PENG ,  Yang LIU ,  Yang DAI ,  Limin ZENG

IPC: C07D401/12 ,  C07D405/14 ,  C07D403/12 ,  A61P35/00 ,  B01J31/24 ,  B01J27/122 ,  B01J31/30

Abstract: An o-aminoheteroaryl alkynyl-containing compound has a structure represented by formula (I), and the compound of formula (I) has advantages of a high FGFR and RET double target inhibitory activity and a relatively low KDR activity, and the compound of formula (I) exhibits a strong inhibitory activity in a human lung cancer cell line NCI-H1581 and a gastric cancer cell line SNU16 as well as an RET-dependent sensitive cell line BaF3-CCDC6-Ret and a mutant thereof. Pharmacokinetic data shows that the o-aminoheteroaryl alkynyl-containing compound has druggability, and exhibits significant relevant inhibition of the growth of related tumors in a long-term animal model of drug efficacy and results in favorable animal condition at effective doses.